Studies have shown that purine-pyrimidine alternating sequences can form a left-handed helical conformation, called Z-DNA. If such sequences exist in natural genomes, they may have great implications in the regulation of gene expression, in the process of cell differentiation, and in carcinogenesis. We have surveyed the potential Z-DNA forming sequences in various eukaryotic genomes. First, we found a large copy number of dT-dG alternating sequence in eukaryotic genomes studies from yeast to human. In fact, two different cloned human actin genes contained (dT-dG)25 and (dT-dG)15. The nucleotide sequence of dT-dG alternating region and its flanking region in various genes indicated that the repeated element consists only of (dT-dG)n. Second, dG-dC alternating sequence was found to be moderately repeated in some eukaryotic genomes, but not detected in others. These results provide the direct evidence for the general and abundant occurrence of potential Z-DNA-forming sequences in natural organisms' genomes. Experiments are now underway to test the hypothesis that Z-DNA sequences may be the regulatory elements for gene expression and the key element in carcinogenesis.